The Chemosensory Recognition of Genetic Individuality Beauchamp, Yamazaki and Boyse

Odor and Genes  The individual odor of an animal is in part determined by its genes  Genes in a chromosomal region in all mammals plays a major part in immunologic recognition  Largely decides the fate of transplanted organs and tissues  MHC = Major Histocompatibility Complex  Mice = H2  Dogs = DLA  Humans = HLA

Olfactory Recognition of Genetic Identity  H-2k and H-2d  k and d stand for the alleles  Alleles = alternative forms of these genes  Places in the genome where mutations occur with remarkable frequency  Two unrelated individual animals are extremely unlikely to have identical MHC types  Why it is difficult to find MHC-matched human organ donors and recipients, except within families  The proteins synthesized by cells of different individuals from instructions encoded by MHC genes are also diverse

Olfactory Recognition of Genetic Identity  Proteins products have carbohydrate chemical groups added = glycoproteins  Inserted into the outer membrane to form surface antigens

Mice Breeding  Inbred Strains  Derived by serial brother-to-sister matings over many generations  To the point of genetic uniformity  Congenic Strains  Derived by first crossing one inbred strain to another  Mate the progeny through many succeeding generations back to mice of the first inbred strain  Then select progeny in each backcross generation for a defined genetic difference  The result is two strains of mice that differ in only one segment of the genetic material  For MHC the congenic strains would be genetically identical except for the region of chromosome 17 that bears the MHC (H-2) group of genes

Congenic Mice ReceiverDonor

Filial Generations  The parental generation is the first set of parents crossed.  The F1 (first filial) generation consists of all the offspring from the parents - their children.  The F2 (second filial) generation consists of the offspring from allowing the F1 individuals to interbreed - the grandchildren of the parental generation.

F2 Linkage Test  A pair of H-2 congenic strains (genetically identical except for H-2) is crossed to produce the F1 generation  F1 – first filial (children)  The F1 population consists of genetically uniform mice that are H-2 heterozygotes  Every F1 mouse carries both the paternal and maternal H-2 alleles  The F1 H-2 heterozygotes are then crossed to give the F2 generation (grandchildren)  The F2 consists of two groups of H-2 homozygotes, each genetically identical with the respective inbred grandparent strain

Mating Preferences  Although the F2 homozygotes are genetically identical with the respective grandparents, they have experienced a different environment with respect to H-2  The H-2 mating preferences of F2 homozygotes were not in all cases identical with the preferences of genetically identical mice of the grandparental strains  The MHC-related mating preferences of mice are at least in part the result of familiar chemosensory imprinting

Basis of Mating Preferences  Mice can sense one another’s H2 types  Favoring partners that differ from themselves at the H2 locus  This bias favors outbreeding and H2 heterozygosity  Promotes diversity of H2 genes  May help the immune system adapt to new threats

Odor  It is well to remember that readily distinguishable compound odors can be generated simply by varying the proportions of the chemical constituents of a given mixture of odorants  Variations in the output of odorous metabolites arising from MHC genetic variation might alone account for individual odors related to MHC types